Comparative Evaluation of [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT in Metastatic Breast and Lung Cancer: Semiquantitative, Volumetric and Prognostic Assessment

Objective: To compare metastatic lesion detection on [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT in metastatic breast and lung cancers and to assess the relationship between PET-derived imaging parameters and progression-free survival (PFS). Methods: In this prospective dual-cohort study, 45 patients (23 breast cancer, 22 lung adenocarcinoma) underwent paired [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT within four weeks. Semiquantitative (SUVmax, SUVmean) and volumetric (MTV, TLG, STV, TLF) PET parameters were measured. Metastatic detection was compared, and correlations with PFS were assessed. Results: In breast cancer, [18F]FDG demonstrated higher primary tumor uptake, whereas [68Ga]Ga-DOTA.SA.FAPi showed lower background activity, resulting in higher tumor-to-background ratios for brain and bone metastases. Whole-body volumetric indices (wbTLG, wbTLF) showed strong inverse correlations with PFS. In lung adenocarcinoma, volumetric FAPi-derived parameters (wbTLF, wbSTV) demonstrated modest but significant correlations with PFS. [68Ga]Ga-DOTA.SA.FAPi PET/CT detected more brain metastases than [18F]FDG PET/CT in both cohorts (breast: 15/15 vs. 8/15; lung: 14/14 vs. 4/14). Conclusions: [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT provide complementary diagnostic and prognostic information. In metastatic breast cancer, FAPi-derived volumetric parameters strongly correlate with PFS and improve detection of brain metastases. In lung adenocarcinoma, [68Ga]Ga-DOTA.SA.FAPi PET/CT offers low background uptake and prognostically relevant stromal metrics. These findings support a potential role for integrating [68Ga]Ga-DOTA.SA.FAPi PET/CT into disease staging, prognostication, and treatment monitoring. This study did not involve prospective assignment to health-related interventions and therefore did not require clinical trial registration.